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Survival extrapolation is an important statistical concept for estimating long-term survival from short-term clinical trial data. It is widely used in health technology assessment (HTA). Survival extrapolation is often performed by fitting one or two parametric models selected based on experience or selecting a model based on some goodness of fit statistics from a predefined collection of models. The main challenge in survival extrapolation is that the result is sensitive to model misspecification. In this study, we aim to propose a new approach that has a robust performance for survival extrapolation.We propose a new method called Ensemble Learning for Survival Extrapolation (ELSE). Instead of selecting one best model from a predefined collection, ELSE builds an ensemble model based on a collection of models from the model library. Under this framework, we construct a point estimate of the long-term survival with a weighted average of the estimates of all candidate models and derive confidence intervals using nonparametric bootstrap.With our extensive numerical simulation studies, the proposed ELSE method shows better performance than the traditionally used model selection procedure based on Akaike Information Criterion (AIC). With a real data application to the Therapeutically Applicable Research to Generate Effective Treatment Wilms Tumor project (TARGET-WT) data, the ELSE method produces better survival extrapolation results in point estimate accuracy and confidence interval coverage.We developed an ensemble learning method for survival extrapolation (ELSE) which is robust for the underline data model and has good real data performance.

Cluster randomized controlled trials (cluster RCTs), also known as parallel-arm group-randomized trials, are trials in which the randomized units are groups of participants, as opposed to individual participants. These trials have largely been implemented to address broad public health issues, but with the growing interest in use of real-world data in the regulatory setting, this design may be increasingly considered for industry trials. The key difference between cluster RCTs and traditional RCTs is the intraclass correlation coefficient (ICC) that needs to be considered in cluster RCTs. In this article, we discuss some key practical considerations that are related to ICC in the design, conduct, analysis, and report stages of a cluster RCT. These key considerations related to ICC can lead to improvement in how we translate research findings from cluster RCTs into practices in the biopharmaceutical industry.

To compare the clinical efficacy of tamoxifen and Chinese patented medicine (Pingxiao capsules) in patients with gynecomastia and discuss the safety of the two treatments. We retrospectively analysed the clinical data of 388 male patients with gynecomastia who were treated in the Outpatient Clinic of our hospital between January 2010 and December 2020. There were 103 patients in the tamoxifen (TAM) group and 103 patients in the Chinese patented medicine group. There were 182 patients in the observation group (non-medication group; age range, 11-75 years; average age, 33.1 years). The natural outcomes were compared between the observation and two medication groups under the same conditions. Disease progression was compared between the observation and two medication groups over the same treatment duration to confirm the efficacy of the medication treatments. Patients with clinical grade 2 gynecomastia accounted for the highest proportion of patients in the TAM group. The percentage of patients with clinical grade 2 gynecomastia was comparable in the Chinese patented medicine and observation groups. The percentage of patients with clinical grades 1 and 3 gynecomastia was the lowest in the TAM group and comparable among the three groups (p = 0.014). The TAM group had the largest number of patients achieving breast shrinkage, and therefore had the best efficacy (p = 0.000). Among the three groups, the surgery rate was the highest in the observation group (p = 0.000). Patients with the greatest glandular tissue thickness achieved better outcomes after medication treatment (p = 0.000). Patients with a higher clinical grade also had a higher surgery rate (p = 0.000). Some patients from the TAM and Chinese patented medicine groups had side effects. TAM results in better outcomes than Chinese patented medicine in gynecomastia patients. The surgery rate is the highest in the observation group. In addition, among some patients with a greater glandular tissue thickness, the higher the clinical grade is, the higher the surgery rate is. Both TAM and Chinese patented medicine cause some side effects and should be used with caution along with continuous follow-up evaluation of patients receiving either treatment.

Randomized controlled clinical trials (RCTs) have been the gold standard for the evaluation of efficacy and safety of medical interventions. However, the costs, duration, practicality, and limited ...

In oncology clinical trials, characterizing the long-term overall survival (OS) benefit for an experimental treatment is often unobservable if some patients in the control group switch to drugs in ...

As real-world data (RWD) become more readily available, the regulatory agencies, medical product developers, and other key stakeholders have increasing interests in exploring the use of real-world ...

Real-world data (RWD), such as electronic health records, reimbursement requests as adjudicated by health insurance companies, and health survey data as collected by government agencies or other re...

Real-world evidence (RWE), derived from data from “real-world” clinical practice and medical product utilization, is an increasingly important source of evidence that holds great potential to incre...

In recent years, breast cancer attracts more and more attention because of its high incidence. To explore the molecular functions and mechanisms, we performed RNA sequencing on the tumor tissues and their paired normal tissues from three breast cancer patients. By differential expression analysis, we found 3764 differentially expressed (DE) mRNAs, 5416 DE lncRNAs, and 148 DE circRNAs. Enrichment analysis suggested that the DE lncRNAs and DE circRNAs were enriched in mitochondria and nucleus, which indicated that they may participate in the vital metabolism directly or indirectly, such as fatty acid metabolism. Subsequently, the protein–protein interaction (PPI) network was constructed and we got 8 key proteins, of which the matrix metalloproteinase-9 (MMP9; degree 5) draws our attention. Based on the 38 up-regulated circRNAs and 14 down-regulated circRNAs, we constructed competing endogenous RNA (ceRNA) networks, from which the has-miR-6794-5p has been identified to enriched in the up-regulated network and correlated with the circNFIX directly. At this point, we presented that the circNFIX and MMP9 may play a significant role by regulating fatty acid metabolism in breast cancer.

Tirofiban can be used to treat patients with acute ischemic stroke (AIS), this study was to evaluate the efficacy and safety of tirofiban combined with heparin in the treatment of mild to moderate AIS. A total of 98 patients with mild to moderate AIS randomly were divided into 2 groups within 48 h: the treatment group treated with tirofiban and, and the control group treated with aspirin + clopidogrel. The treatment group was given the same scheme as the control group after the treatment of tirofiban combined with heparin for 48 h. It was found that, compared with the control group, a significant decreased National Institute of Health stroke scale (NIHSS) was found in 48 h and 14 d, especially to the Barthel index (BI) in the treatment group (P 0.05). Furthermore, Modified Rankin Scale (MRS, ≤2) in the treatment group was significantly upregulated in 90 d (P 0.05). However, there were no significant differences in the adverse drug reactions between the two groups. It was indicated that nerve function and long-term prognosis in patients undergoing heparin for mild to moderate AIS were obviously improved than the control group.

Gynecomastia is the most common benign disease in males with an increasing prevalence in recent years. It may cause local pain and psychological disorders. The vacuum-assisted breast biopsy system has been reported to be a novel surgical approach for the treatment of gynecomastia. However, there are little detailed reports comparing the curative effect between traditional surgery and vacuum-assisted breast biopsy for gynecomastia. Besides, there was little study which compared the application of two different systems for the treatment of gynecomastia. Our study aimed to investigate the effectiveness of vacuum-assisted breast biopsy systems for patients with gynecomastia. We retrospectively reviewed 83 patients with gynecomastia between January 2015 and December 2019. Open surgery was performed in 56 patients, and vacuum-assisted breast biopsy was performed in 27 patients. The characteristics of patients as well as the curative effects between the two groups were analyzed. The two vacuum-assisted breast biopsy systems (Mammotome and Encor) were performed for the patients with gynecomastia. The efficacy, safety, complications, and patient satisfactions were recorded during postoperative follow-up periods. Compared with the open surgery group, the vacuum-assisted breast biopsy group had significantly smaller scar sizes left after the operation (5.5 ± 1.3 cm vs 0.8 ± 0.2 cm, p

In order to solve the problem that highway development needs to cross environmentally protected areas, which results in the cutting off of wildlife habitats and fragmentation of the biosphere, on-road biological passages are established in many places. This paper carries out a numerical analysis of the biased load, caused by the backfill of the biological channel, the environment, and the seepage problem of the backfill under rainfall conditions. By comparing the pore water pressure’s test data in backfill with the modeling result data, the influence law of biased pressure load on open hole lining during running period, and the law of water pressure change are derived. The analysis shows that: (1) the backfill soil has a restraining effect on the double-arch tunnel, and the side arch ring’s deformation of the backfill decreases with the increase of the height of the backfill; when backfilling on both sides is flush with the top of the cave and continuing to backfill at the cave’s top, the arch ring near the higher mountain deforms greater because of the mountain’s pressure. (2) The internal force of the channel and the temperature are closely relevant, and the value is gradually stable without the influence of construction or other causes. (3) Pore water pressure variation correlates with seasons: the water pressure is lower in winter and higher in summer. After the pore water is saturated, the monitoring data does not change with the increase of rainfall.

Confounding adjustment plays a key role in designing observational studies such as cross-sectional studies, case-control studies, and cohort studies. In this article, we propose a simple method for sample size calculation in observational research in the presence of confounding. The method is motivated by the notion of E-value, using some bounding factor to quantify the impact of confounders on the effect size. The method can be applied to calculate the needed sample size in observational research when the outcome variable is binary, continuous, or time-to-event. The method can be implemented straightforwardly using existing commercial software such as the PASS software. We demonstrate the performance of the proposed method through numerical examples, simulation studies, and a real application, which show that the proposed method is conservative in providing a slightly bigger sample size than what it needs to achieve a given power.

Randomized controlled clinical trials are the gold standard for evaluating the safety and efficacy of pharmaceutical drugs, but in many cases their costs, duration, limited generalizability, and ethical or technical feasibility have caused some to look for real-world studies as alternatives. On the other hand, real-world data may be much less convincing due to the lack of randomization and the presence of confounding bias. In this article, we propose a statistical roadmap to translate real-world data (RWD) to robust real-world evidence (RWE). The Food and Drug Administration (FDA) is working on guidelines, with a target to release a draft by 2021, to harmonize RWD applications and monitor the safety and effectiveness of pharmaceutical drugs using RWE. The proposed roadmap aligns with the newly released framework for FDA's RWE Program in December 2018 and we hope this statistical roadmap is useful for statisticians who are eager to embark on their journeys in the real-world research.

It has been previously reported that the blockade of interleukin-7 receptor (IL-7R) promotes functional recovery following spinal cord injury (SCI), however, the direct function and molecular mechanism of IL-7 involved in this pathogenic process are unclear. Here, we report that, contrary to IL-7R blockade, the intraspinal administration of IL-7 limits functional recovery following SCI. In addition, IL-7 treatment promotes neuronal apoptosis in spinal cord lesions, which may be attributed to exacerbated focal inflammatory response, as shown by increased accumulation of activated microglia/macrophage and production of proinflammatory mediators. Moreover, IL-7 treatment activates JAK/STAT5 pathway following SCI. At last, more importantly, the pharmacological inhibition of STAT5 abrogates the effects of IL-7 treatment on functional recovery, neuronal apoptosis and focal inflammatory response, suggesting that the effects of IL-7 treatment following SCI are dependent on activating the JAK/STAT5 pathway. Overall, this study reveals the JAK/STAT5 pathway-dependent detrimental role of IL-7 following SCI, and also implies that targeting the IL-7/JAK/STAT5 axis may represent a potential therapeutic approach for SCI treatment.

The objective of this study is to evaluate the rheological properties of styrene-butadiene-styrene and Sasobit modified asphalt binder blended with various contents (0%, 1%, 3% and 5%) of nano-tita...

In this study, the failure mode of flexible reinforced soil slopes under earthquake action was investigated by shaking table tests. The distribution law of a potential failure surface of a flexible no-faceplate reinforced soil slope under earthquake action was obtained based on the analysis results. A simplified trilinear failure surface suitable for flexible reinforced soil slopes without faceplate was proposed. Subsequently, based on the upper-bound theorem of limit analysis, we derived the formula for calculating the yield seismic acceleration coefficient of a flexible no-faceplate reinforced soil slope under a seismic load. The main parameters that affect its seismic performance were determined. The flexible geogrid reverse-packed reinforced earth structure can effectively limit the fracture of a slope body and improve the stability of the slope. This provides a theoretical basis for facilitating the engineering of flexible reinforced soil slopes.

In recent years, there has been a proliferation of regulatory and industry-wide initiatives on structured benefit-risk (BR) assessment. Examples of structured BR frameworks include the PrOACT-URL (Problem formulation, Objectives, Alternatives, Consequences, Trade-Offs, Uncertainties, Risk Attitude and Linked Decisions) from European Medicines Agency Work Package 3, multiple U.S. Food and Drug Administration guidance documents on benefit-risk assessment for medical devices, and U.S. Food and Drug Administration implementation plans for benefit-risk assessment in drug regulatory decision-making. In June 2016, the ICH Expert Working Group finalized the Common Technical Document (CTD) Section 2.5.6 on Benefit-Risk Evaluations. As a result of these efforts, the uptake and utilization of structured benefit-risk (BR) assessments has been increasing. However, the aforementioned BR frameworks are mostly qualitative in nature, and the utility of quantitative BR approaches has not been systemically explored, creating uncertainty about settings in which quantitative BR assessment (qBRA) could be optimally applied. In this paper, we will provide an overview of the current qBRA methods, discuss challenges of qBRA, and describe a structural qBRA framework. The performance of the described qBRA framework will be evaluated by simulations based on a case study.

Data monitoring committees (DMCs), or data and safety monitoring boards, protect clinical trial participants by conducting benefit-risk assessments during the course of a clinical trial. These evaluations may be improved by broader access to data and more effective analyses and presentation. Data monitoring committees should have access to all data, including efficacy data, at each interim review. The DMC reports should include graphical presentations that summarize benefits and harms in efficient ways. Benefit-risk assessments should include summaries that are consistent with the intention-to-treat principle and have a pragmatic focus. This article provides examples of graphical summaries that integrate benefits and harms, and proposes that such summaries become standard in DMC reports.

Warm Mix Asphalt (WMA) is a valued and effective technology to decrease asphalt binder’s viscosity in order to save energy and to reduce the release of carbon dioxide (CO2). Sasobit (an organic additive) is a widely used warm mix additive, which has been studied in several aspects by some researchers such as the increase of physical properties as well as the increase of rheological properties of asphalt binder. Deurex (natural sugar cane wax or free of paraffins), which is similar to the Sasobit, can be seen as a new warm mix additive. The study aims to assess the high temperature rheological properties and viscosity reduction of asphalt which is modified with the two additives: Sasobit and Deurex. During the study, Deurex was added into the base asphalt in same proportion as the Sasobit as 0%, 1%, 2% and 3%, so 16 different binders could be obtained. Above all, the study conducted the Rotational viscometer test (RV), which separately and together measured the two additives’ effects for the viscosity of the binders. The conventional tests results reveal that adding Deurex to the Sasobit can improve the cracking properties of binders as compared to the Sasobit at low temperature. And the viscometer test results reveal that both Sasobit and Deurex can reduce the viscosity and the Sasobit can be more effective than Deurex when the content of additive is low. Furthermore, the decrease of asphalt binders’ viscosities is more obvious at lower temperature. Then the study conducted the Dynamic shear rheometer (DSR) test including the Performance grade, frequency sweep and temperature sweep tests. G∗(complex shear modulus) and δ (phase angle) can be measured in the test, and the results reveal that the Sasobit and Deurex increase the value of G∗ and decrease the value of δ. Therefore, the rutting factor G∗/sinδ is improved. In other words, the high temperature properties of modified asphalt binders are increased, particularly the ability of resistance to deformation. The test also found that the 2%Deurex play a relatively big efficacy with Sasobit. Finally, the Fourier transform infrared spectroscopy (FTIR) test was used to analyze the modification mechanism of the modified binders. All in all, the Sasobit and Deurex modified asphalt do have a good performance in high temperature. And 2%Deurex with 2% or 3%Sasobit is recommend.

The Warm mix asphalt (WMA) industry has attracted considerable attention due to the additives’ability to reduce the mixing and compaction temperatures of the asphalt mixture. Deurex has showed its ...

The purpose of this study aims at investigating the effect of warm-mix additive Sasobit/Deurex on properties of APAO modified asphalt binder (AMB). The physical properties were measured through penetration, softening point and ductility tests. Besides, rotational viscosity (RV), dynamic shear rheometer (DSR) and bending beam rheometer (BBR) test were utilized to determine the rheological characteristics of warm-mix asphalt binders before and after aging. Fourier transform infrared spectroscopy (FTIR) test was used to describe the chemical characteristics of Sasobit/Deurex warm-mixed APAO modified asphalt binder (AMB). The results showed that incorporation of Sasobit/Deurex into AMB could effectively reduce the viscosity and exert a distinct modification on high temperature performance of asphalt binders in terms of reduced penetration, increased softening point and decreased ductility. Dynamic shear rheometer (DSR) test showed that warm-mix asphalt had bigger complex modulus and smaller phase angle than blank AMB. Bending beam rheometer (BBR) test indicated that minor addition of Deurex (2%) have improved the low temperature rheological performance of AMB while Sasobit had negative effect on it. Moreover, the FTIR analysis showed that chemical reactions might happen during the mixing of Sasobit/Deurex with AMB. In overall consideration, 4% Sasobit and 2% Deurex were optimal dosages for the AMB in this experiment concerning the rheological characteristics, construction workability and economic benefits.

The field of structured benefit-risk assessment has evolved rapidly in the last few years with a great deal of regulatory and industry-wide initiatives. The available structured approaches to benefit-risk assessments exhibit and share many common elements in terms of defining the decision problem and therapeutic context, identifying key benefit and risk factors, and interpreting and communicating benefit-risk findings. However, there is limited guidance with these initiatives that is specific to metrics and methods to conduct benefit-risk assessment. Although we agree that benefit-risk metrics and analysis methods may be specific to individual clinical settings, we believe that there are general principles that can be followed. In this article, we propose a stepwise quantitative approach for benefit-risk assessment. We applied the stepwise quantitative approach to 3 real case studies.

The seismic behavior of an embedded concrete-filled steel tubes (CFST) precast column-to-cap beam socket connection of a practical engineering project was investigated through 1:3-scale quasi-static tests. The precast column and cap beam was integrated by ultrahigh-performance concrete (UHPC) grouting to improve the interface bonding behavior and lateral constraint. The influences of embedment depth, socket forming method, and column section size on the cyclic response of the structure were evaluated. The experimental results revealed that when the concrete-filled steel tube (CFST) embedded depth is 1.0 times tube diameter, the specimens can obtain good strength and hysteresis performance. The socket hole formed by a steel pile can further promote the hysteresis performance of the cap beam-column joint, and the ultimate failure of the joint is the fracture of the column longitudinal rebar. A model for evaluating the moment capacity of the CFST socket connection was proposed and verified by the test results, which can be used in the preliminary design the proposed connection.

The draft adaptive design guidance released by FDA in 2010 included references to adaptive study designs that were described as "less well-understood." At that time, there was relatively little regulatory experience with such designs, and their properties were felt to be insufficiently understood. In order to promote greater use of adaptive designs, especially those categorized as less well-understood, the Best Practice Subteam of the DIA Adaptive Designs Scientific Working Group (ADSWG) has worked on describing and characterizing these designs, identifying challenges associated with them and suggesting improvements to design or study conduct aspects that might make them more acceptable. This paper summarizes the work from the subteam.

Adaptive design (AD) clinical trials use accumulating subject data to modify the parameters of the design of an ongoing study, without compromising the validity and integrity of the study. The 2010 US Food and Drug Administration (FDA) Draft Guidance on Adaptive Design Clinical Trials described a subset of 7 primary design types as "less well-understood." FDA defined these designs as those with limited regulatory experience. To better understand the properties of these less well-understood ADs and to promote their use when applicable, the Best Practices Subteam for DIA's Adaptive Design Scientific Working Group conducted an extensive nonsystematic search and reviewed trials from multiple sponsors who had employed these designs. Here, we review 10 specific case studies for which less well-understood ADs were employed and share feedback about their challenges and successes, as well as details about the regulatory interactions from these trials. We learned that these designs and associated statistical methodologies can make difficult research situations more amenable for study and, therefore, are needed in our toolbox. While they can be used to study many diseases, they are particularly valuable for rare diseases, small populations, studies involving terminal illnesses, and vaccine trials, in which it is important to find efficient ways to bring effective treatments to market more rapidly. It is imperative, however, that these methodologies be utilized appropriately, which requires careful planning and precise operational execution.

Benefit-risk (BR) assessment is important to ensure safety and effectiveness of medical projects in clinical development and post marketing surveillance. The evaluation of the balance between benefits and risks of a drug is fundamental to all stakeholders involved in the development, registration, and use of drugs. Many quantitative approaches have been developed that may draw together data from different sources to present them in ways that can aid decision-making. Among these quantitative approaches, multicriteria decision analysis (MCDA) is one of the most useful approaches, since it provides a framework for systematic and replicable analyses of complex decision problems involving value tradeoffs. In most real-life situations, decision makers are not able to get exact preference information (weights). To overcome this limitation of MCDA, a method called stochastic multicriteria acceptability analysis (SMAA) was proposed as a quantitative approach to BR assessment in drug development. The chief ...

A structured benefit-risk assessment (BRA) is critical for drug development and lifecycle management. How to select B-R endpoints, determine weighting for these endpoints, and evaluate uncertainties are key aspects of the B-R decision-making process. In this article, we discuss key considerations on endpoint selection, challenges of double counting and correlated endpoints, and methods that can be used to address these challenges. In addition, we discuss the use of qualitative and quantitative weighting in BRA, techniques useful for weight construction, and weights based on empirical preferences. Potential sources for uncertainties in BRA, the approaches to illustrate and to address these uncertainties are described. Finally, we emphasize that benefit-risk assessment is a continuous process and requires cross-functional efforts.

When providing advice on a medical product, a major task for FDA advisory committee members is to determine whether or not the benefits of the product under discussion outweigh its risks. Thoughtful and creative utilization of analysis methods and visualization tools often helps the sponsors and the FDA to clearly and succinctly deliver the key message, that is, whether the benefit-risk profile is favorable or unfavorable. In this article, we summarize a review of analysis methods and visual tools that were included in recent (during 2011–2014) FDA advisory committee meeting materials. We summarize the key findings related to benefit-risk (B-R) evaluations. Illustrative examples of analysis and visualization tools are provided along with potential refinements to provide readers' proper context for the appropriate use of various B-R tools in practice when evaluating the B-R balance of medical products.

The benefit-risk assessment of a new medicinal product or intervention is one of the most complex tasks that sponsors, regulators, payers, physicians, and patients face. Therefore, communicating the trade-off of benefits and risks in a clear and transparent manner, using all available evidence, is critical to ensure that the best decisions are made. Several quantitative methods have been proposed in recent years that try to provide insight into this challenging problem. Bayesian inference, with its coherent approach for integrating different sources of information and uncertainty, along with its links to optimal decision theory, provides a natural framework to perform quantitative assessments of the benefit-risk trade-off. This paper describes the current state of the art in Bayesian methodologies for quantitative benefit-risk assessment, and how these may be leveraged throughout the life cycle of a medicinal product to support and augment clinical judgment and qualitative benefit-risk assessments. Gaps and potential new directions that extend the current approaches are also identified.

Pharmaceutical drugs and devices are increasingly evaluated by quantitative tools that combine benefit and risk. These tools vary by their limitations and desirable properties, which may confuse the decision-making process. Experts from the Food and Drug Administration (FDA) and industry shared their perspectives at the 2012 American Statistical Association (ASA) Biopharmaceutical Section FDA-Industry Statistics Workshop, and these insights are presented here. First, benefit-risk terminology is given to better understand subtle distinctions. Next, pragmatic considerations in endpoint selection are given that distinguish between benefit-risk assessment and analysis of clinical trials. Then the strengths of weighting methods, including ranking, utilities, and risk tolerance for assessing the trade-off between benefits and risks, are compared. The last topic presented is summarizing information to ease the interpretation, transparency, and ability to support decisions. Benefit-risk methods are moving towards a unified paradigm to make selection of endpoints, weights, and metrics easier and more structured. This will lead to better decision-making based on a transparent assessment and clear interpretability.

Accelerated bridge construction (ABC) has been paid great attention in China for the significant advantages compared with cast-in-place (CIP), such as higher construction speed, less environmental impact and structural members of higher quality. However, the reliability, durability and seismic behavior of the connection between prefabricated bridge column and the rest of the structure are primary factors that limit the application of the ABC in the moderate and high seismic zones. In this study, quasi-static experimental investigation of seismic performance of three 1:3-scale ultra-high performance concrete (UHPC)-filled socket reinforced concrete (RC) column-foundation connection specimens were conducted. A fiber-based finite element model is developed considering the rotation effect of the column embedded in the footing. The seismic behavior of the precast column specimens with UHPC-filled socket connection type was compared with that of CIP specimen. The experimental and numerical results show that the damage evolution, failure modes and hysteretic responses of the precast bridge column are equivalent with those of the CIP bridge column. Numerical analysis also validated that the finite element model(FEM) in this paper is adequate to predict seismic response of the precast column with UHPC-filled socket connection. The UHPC-filled socket connection is a reliable connection type in prefabricated column-foundation connection joint which is suitable for moderate and high seismic regions.